The proposed study aims to analyze the neuro-endocrine mechanisms which regulate the programmed death in a unique model, Petromyzon marinus. In this lamprey a chain of events leads to death a few weeks after a single act of spawning. The "terminal program" seems to begin with metamorphosis to the adult stage and involves: (1) a complete disappearance of gall bladder and bile ducts, from which time the animals fast, and their intestine shows progressive atrophy; (2) a progressive kidney degeneration which culminates at the end of the animals' life; (3) changes in the pituitary structure which require further analysis; (4) a continuous proliferation of the islets of Langerhans with the appearance of 3 new cell types in addition to the B-cells. Contrary to the stress-related death of salmons of the genus Oncorhynchus, death of the lamprey occurs in the absence of both hypercorticism and the hyperglycemic hormone glucagon. The available evidence suggests that neuro-endocrine mechanisms control the final events in the lamprey's life. This investigation will combine (1) an identification of postmetamorphic alterations in the central nervous, endocrine, digestive, urinary and cardiovascular systems with (2) an experimental manipulation of these changes by lesions in the central nervous system, endocrinectomies (pineal, pituitary, gonads, islet organ) and steroid hormone implantations. Methods will include (1) measurement of selected blood parameters (such as blood cell variations, hematocrit, selected metabolites and electrolytes); (2) histological, histochemical and ultrastructural studies of the above mentioned organ systems, with particular attention being paid to (a) activity changes in endocrines and neurosecretions, (b) degenerative changes in the central nervous system, (c) atrophies in the digestive system, (d) kidney regression, (e) vascular pathologies; (3) autoradiography of steroid hormone and thyroxin target cells in the central nervous and endocrine systems, and in organs with obvious morphological changes; (4) measurement of changes in selected tissue parameters (such as water, protein, lipids, glycogen and electrolytes). It is expected that this study, which combines the expertise of four laboratories, will provide a comprehensive analysis of the mechanisms controlling programmed death.